Background
Materials and methods
Patients and samples
Sample sequencing and data analysis
Diagnostic assessment of mNGS
Statistics analysis
Results
General characteristics
CNS infection (159) | Non-CNS infection (71) | p value | |
---|---|---|---|
CNS infection (n) | |||
Bacterial infection | 95 | – | – |
Viral infection | 38 | – | – |
Parasitic infection | 3 | – | – |
Fungal infection | 10 | – | – |
Mixed infectiona | 4 | – | – |
Unclassified | 9 | – | – |
Non-CNS infection(n) | |||
Autoimmune encephalitis | – | 13 | – |
Malignant tumor | – | 13 | – |
Pulmonary diseases | – | 6 | – |
Tsutsugamushi disease | – | 1 | – |
Local infection | – | 7 | – |
Blood-stream infection | – | 1 | – |
Hematological disease | – | 3 | – |
Rheumatic disease | – | 2 | – |
Psychological disease | – | 1 | – |
Fever of unknown origin | – | 7 | – |
Other neurological diseaseb | – | 17 | – |
Gender(n) | 0.791 | ||
Male | 97 | 42 | |
Female | 62 | 29 | |
Age, year (range) | 44.39 (13.00–73.00) | 42.30 (15.00–84.00) | 0.175 |
Body temperature, °C (Range) | 37.61 (36.20–40.70) | 37.47 (36.10–39.60) | 0.695 |
Empirical treatment history(n) | 0.103 | ||
Yes | 119 | 60 | |
No | 40 | 11 | |
Blood laboratory examination (range) | |||
C-reaction protein, mg/L | 19.6 (3.0–126.0) | 32.8 (3.0–194.0) | 0.568 |
Erythrocyte sedimentation rate, mm/h | 25.20 (2.00–137.00) | 26.07 (2.00–118.00) | 0.830 |
Procalcitonin, ng/mL | 0.34 (0.01–4.90) | 0.19 (0.02–1.82) | 0.386 |
Serum ferritin, ng/mL | 631.84 (14.46–2000.00) | 560.26 (64.92–1209.00) | 0.802 |
WBC, *109/L | 8.84 (2.35–26.03) | 9.06 (2.87–27.60) | 0.347 |
Neutrophil, % | 69.26 (26.00–95.70) | 79.11 (60.4–97.30) | 0.427 |
Overall diagnostic performance of mNGS
Sensitivity compared to culture | Specificity compared to clinical diagnosis | ||
---|---|---|---|
Without empirical treatment | With empirical treatment | ||
mNGS | 90.00% (9/10) | 66.67% (6/9) | 98.59% (70/71) |
Culture | – | – | 100.00% (71/71) |
Conventional methods | – | – | 100.00% (71/71) |
Detection rate | No history of empirical treatment (%, 95% CI) | History of empirical treatment (%, 95% CI) | P value between patients treated or not (%, 95% CI) |
---|---|---|---|
Detection rate of CNS infections (n = 159) | |||
mNGS | 50.00% (20/40) (34.06–65.94) | 34.45% (41/119)a (26.14–43.79) | 0.0802 |
Culture | 25.00% (10/40) (13.25–41.52) | 7.56% (9/119)a (3.74–14.27) | 0.003 |
Conventional methods | 40.00% (16/40) (25.28–56.61) | 18.49% (22/119)a (12.19–26.87) | 0.006 |
Combined methods | 55.00% (22/40) (38.66–70.40) | 39.50% (47/119) (30.78–48.90) | 0.087 |
Bacterial infections (n = 99) | |||
mNGS | 57.14% (16/28)b (37.43-74.97) | 38.03% (27/71)c,d (27.00–50.36) | 0.084 |
Culture | 21.43% (6/28)b (9.03–41.46) | 11.27% (8/71)c (5.34–21.53) | 0.324 |
Conventional methods | 39.29% (11/28) (22.13–59.27) | 15.49% (11/71)d (8.35–26.46) | 0.010 |
Combined methods | 60.71% (17/28)b (40.73–77.87) | 42.25% (30/71)c,d (30.81–54.54) | 0.0976 |
Viral infections (n = 41) | |||
mNGS | 14.29% (1/7) (0.75–57.99) | 23.53% (8/34) (11.38–41.57) | > 0.9999 |
Culture | N/A | N/A | N/A |
Conventional methods | 0.00% (0/7) (0.00–43.91) | 17.65% (6/34) (7.39–35.17) | 0.567 |
Combined methods | 14.29% (1/7) (0.75–57.99) | 23.53% (8/34) (11.38–41.57) | 0.971 |
Fungal infections (n = 11) | |||
mNGS | 83.33% (5/6) (36.48–99.12) | 60.00% (3/5) (17.04–92.74) | 0.545 |
Culture | 83.33% (5/6) (36.48–99.12) | 20.00% (1/5) (1.05–70.12) | 0.080 |
Conventional methods | 100.00% (6/6) (51.68–100.00) | 60.00% (3/5) (17.04–92.74) | 0.182 |
Combined methods | 100.00% (6/6) (51.58–100.00) (46.29-100.00) | 100.00% (5/5) (46.29–100.00) | > 0.9999 |
Parasitic infections (n = 3) | |||
mNGS | N/A | 66.7% (2/3) | N/A |
Culture | N/A | N/A | N/A |
Conventional methods | N/A | 66.7% (2/3) | N/A |
Combined methods | N/A | 66.7% (2/3) | N/A |
mNGS positive/Case consistent (a) | mNGS positive/Case inconsistent (b) | mNGS negative/Case inconsistent (c) | mNGS negative/Case consistent (d) | p value among all groups (Mann–Whitney test) | p value between group a and c (Mann–Whitney test) | p value between group a and d (Mann–Whitney test) | |
---|---|---|---|---|---|---|---|
Suspected CNS infections (a = 61; b = 7; c = 98; d = 70) | |||||||
CSF WBC,*106/L (Median(Range)) | 130 (1–26,000) | 60 (1–110) | 68 (1–1630) | 7 (0–340) | 0.001* | 0.002* | < 0.0001* |
CSF protein, mg/L (Median(Range)) | 1741.0 (209.0–15,000.0) | 839.5 (208.0–5477.0) | 1351.0 (33.0–15,000.0) | 686.0 (208.0–13,223.0) | 0.065 | 0.002* | < 0.0001* |
CSF/serum glucose ratio (Mean (Range)) | 0.36 (0.06–0.71) | 0.37 (0.24–0.5) | 0.42 (0.10–0.75) | 0.60 (0.13–1.19) | 0.023* | 0.003* | < 0.0001* |
CSF Cl, mmol/L (Mean(Range)) | 115.65 (97.00–143.00) | 119.50 (104.00–130.00) | 116.81 (92.00–130.00) | 118.52 (96.00–132.00) | 0.845 | 0.110 | 0.29 |
CSF pressure, mmH2O (Mean(Range)) | 198.16 (50.00–300.00) | 159.40 (70.00–300.00) | 194.19 (88.00–300.00) | 185.47 (80.00–300.00) | 0.598 | 0.794 | 0.24 |
Bacteria (a = 43; b = 5; c = 56; d = 126) | |||||||
CSF WBC, *106/L (Median(Range)) | 138 (1–26,000) | 40 (1–110) | 68 (4–1630) | 20 (0–730) | 0.000 * | 0.029* | < 0.0001* |
CSF protein, mg/L (Median (Range)) | 1845.5 (209.0–14,224.0) | 1112.0 (208.0–2499.0) | 1100.0 (33.0–15,000.0) | 867.0 (208.0–15,000.0) | 0.118 | 0.115 | 0.000* |
CSF/serum glucose ratio (Mean(Range)) | 0.29 (0.06–0.52) | 0.42 (0.31–0.55) | 0.41 (0.19–0.75) | 0.53 (0.10–1.19) | 0.085 | 0.001* | < 0.0001* |
CSF Cl, mmol/L (Mean(Range)) | 115.32 (98.00–131.00) | 117.20 (104.00–122.00) | 114.96 (92.00–126.00) | 118.49 (96.00–143.00) | 0.680 | 0.677 | 0.076 |
CSF pressure, mmH2O (Mean(Range)) | 212.68 (92.00–300.00) | 135.00 (70.00–215.00) | 192.48 (88.00–300.00) | 188.01 (50.00–300.00) | 0.153 | 0.286 | 0.114 |
Virus (a = 9; b = 2; c = 32; d = 187) | |||||||
CSF WBC,*106/L (Median(Range)) | 161 (45–300) | 121 (2–242) | 35 (1–570) | 46 (0–26000) | 0.724 | 0.019* | 0.116 |
CSF protein, mg/L (Median(Range)) | 1657.0 (662.0–6459.0) | 1036.5 (671.0–1456.0) | 937.5 (208.0–6741.0) | 1066.0 (33.0–15,000.0) | 0.190 | 0.012 | 0.125 |
CSF/serum glucose ratio (Mean(Range)) | 0.44 (0.36–0.59) | 0.50 (0.39–0.62) | 0.48 (0.31–0.73) | 0.45 (0.06–1.19) | 0.994 | 0.299 | 0.539 |
CSF Cl, mmol/L (Mean(Range)) | 117.57 (100.00–131.00) | 123.50 (113.00–134.00) | 119.61 (104.00–143.00) | 116.49 (92.00–132.00) | 0.785 | 0.579 | 0.527 |
CSF pressure, mmH2O (Mean(Range)) | 194.17 (100.00–230.00) | 140.00 (85.00–195.00) | 191.35 (100.00–300.00) | 192.28 (50.00–300.00) | 0.772 | 0.935 | 0.812 |
Fungi (a = 8; b = 0; c = 3; d = 219) | |||||||
CSF WBC, *106/L (Median(Range)) | 115 (70–730) | N/A | 2 (2–15) | 44 (0–26,000) | 0.902 | 0.238 | < 0.0001* |
CSF protein, mg/L (Median (Range)) | 1122.5 (520.0–15,000.0) | 1480.0 (1401.0–1484.0) | 1060.0 (33.0–7098.0) | 0.145 | 0.548 | 0.377 | |
CSF/serum glucose ratio (Mean(Range)) | 0.33 (0.16–0.52) | 0.40 (0.24–0.52) | 0.46 (0.06–1.19) | 0.774 | 0.548 | 0.093 | |
CSF Cl, mmol/L (Mean(Range)) | 111.83 (97.00–122.00) | 122.33 (116.00–130.00) | 117.18 (92.00–143.00) | 0.684 | 0.381 | 0.461 | |
CSF pressure, mmH2O (Mean(Range)) | 170.00 (50.00–300.00) | 146.67 (130.00–160.00) | 193.15 (70.00–300.00) | 0.403 | 0.786 | 0.611 | |
Parasite (a = 2; b = 0; c = 1; d = 227) | |||||||
CSF WBC, *106/L (Median(Range)) | 34 (9–58) | N/A | 0 (N/A) | 50 (0–26,000) | 0.947 | N/A | 0.686 |
CSF protein, mg/L (Median(Range)) | 959.0 (506.0–1412.0) | 181.0 (N/A) | 1079.5 (33.0–15,000.0) | 0.682 | 0.706 | ||
CSF/serum glucose ratio (Mean(Range)) | 0.36 (0.29–0.42) | 0.65 (N/A) | 0.46 (0.06–1.19) | 0.879 | 0.458 | ||
CSF Cl, mmol/L (Mean(Range)) | 119.50 (111.00–128.00) | 127.00 (N/A) | 117.04 (92.00–143.00) | 0.843 | 0.703 | ||
CSF pressure, mmH2O (Mean(Range)) | 222.50 (150.00–295.00) | 135.00 (N/A) | 191.13 (50.00–300.00) | 0.588 | 0.697 |